View source for CYP1A1

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'''Cytochrome P450, family 1, subfamily A, polypeptide 1''' is a [[protein]]<ref name="pmid10493257">{{cite journal | author = Kawajiri K | title = CYP1A1 | journal = IARC scientific publications | volume = | issue = 148 | pages = 159–72 | year = 1999 | pmid = 10493257 | doi = | url = | issn = }}</ref> which in humans in encoded by the '''''CYP1A1''''' [[gene]].<ref name="pmid15128046">{{cite journal | author = Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW | title = Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants | journal = Pharmacogenetics | volume = 14 | issue = 1 | pages = 1–18 | year = 2004 | month = January | pmid = 15128046 | doi = | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0960-314X&volume=14&issue=1&spage=1 | issn = }}</ref> The protein a member of the [[cytochrome P450]] superfamily of enzymes.<ref name="pmid9890157">{{cite journal | author = Smith G, Stubbins MJ, Harries LW, Wolf CR | title = Molecular genetics of the human cytochrome P450 monooxygenase superfamily | journal = Xenobiotica; the fate of foreign compounds in biological systems | volume = 28 | issue = 12 | pages = 1129–65 | year = 1998 | month = December | pmid = 9890157 | doi = | url = | issn = }}</ref>

==Function==
CYP1A1 is involved in phase I [[xenobiotic]] and [[drug metabolism]] (one substrate of it is [[theophylline]]). It is inhibited by [[fluoroquinolone]]s and  [[macrolide]]s and induced by [[aromatic hydrocarbons]].<ref name="pmid8313840">{{cite journal | author = Beresford AP | title = CYP1A1: friend or foe? | journal = Drug metabolism reviews | volume = 25 | issue = 4 | pages = 503–17 | year = 1993 | pmid = 8313840 | doi = | url = | issn = }}</ref>

CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons ([[polycyclic aromatic hydrocarbons]], PAH), for example, [[benzopyrene|benzopyrene]] (BP), by transforming it to an [[epoxide]]. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by [[epoxide hydrolase]] (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate [[carcinogen]].<ref name="pmid8313840"/>

==Regulation==
The expression of the CYP1A1 and CYP1B1 genes are regulated by the [[aryl hydrocarbon receptor]], a ligand activated [[transcription factor]].<ref name="pmid17431034">{{cite journal | author = Ma Q, Lu AY | title = CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies | journal = Drug metabolism and disposition: the biological fate of chemicals | volume = 35 | issue = 7 | pages = 1009–16 | year = 2007 | month = July | pmid = 17431034 | doi = 10.1124/dmd.107.015826 | url = | issn = }}</ref>

==Polymorphisms==
Several [[polymorphism (biology)|polymorphism]]s have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 [[polymorphism]]s include:<ref name="pmid1707592">{{cite journal | author = Petersen DD, McKinney CE, Ikeya K, Smith HH, Bale AE, McBride OW, Nebert DW | title = Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP | journal = American journal of human genetics | volume = 48 | issue = 4 | pages = 720–5 | year = 1991 | month = April | pmid = 1707592 | pmc = 1682951 | doi = | url = | issn = }}</ref><ref name="pmid7901425">{{cite journal | author = Cosma G, Crofts F, Taioli E, Toniolo P, Garte S | title = Relationship between genotype and function of the human CYP1A1 gene | journal = Journal of toxicology and environmental health | volume = 40 | issue = 2-3 | pages = 309–16 | year = 1993 | pmid = 7901425 | doi = | url = | issn = }}</ref><ref name="pmid8001264">{{cite journal | author = Crofts F, Taioli E, Trachman J, Cosma GN, Currie D, Toniolo P, Garte SJ | title = Functional significance of different human CYP1A1 genotypes | journal = Carcinogenesis | volume = 15 | issue = 12 | pages = 2961–3 | year = 1994 | month = December | pmid = 8001264 | doi = | url = http://carcin.oxfordjournals.org/cgi/content/abstract/15/12/2961 | issn = }}</ref><ref name="pmid8609043">{{cite journal | author = Kiyohara C, Hirohata T, Inutsuka S | title = The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene | journal = Japanese journal of cancer research : Gann | volume = 87 | issue = 1 | pages = 18–24 | year = 1996 | month = January | pmid = 8609043 | doi = | url = | issn = }}</ref>
* M1, [[thymine|T]]→[[cytosine|C]] substitution at [[nucleotide]] 3801 in the 3'-[[non-coding RNA|non-coding]] region
* M2, [[adenine|A]]→[[guanine|G]] substitution at nucleotide 2455 leading to an amino acid change of [[isoleucine]] to [[valine]] at [[Codon#RNA_codon_table|codon]] 462
* M3, [[thymine|T]]→[[cytosine|C]] substitution at nucleotide 3205 in the 3'-non-coding region
* M4, [[cytosine|C]]→[[adenine|A]] substitution at nucleotide 2453 leading to an amino acid change of [[threonine]] to [[asparagine]] at codon 461
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==References==
{{Reflist|2}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Nelson DR, Zeldin DC, Hoffman SM, ''et al.'' |title=Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. |journal=Pharmacogenetics |volume=14 |issue= 1 |pages= 1–18 |year= 2004 |pmid= 15128046 |doi=  }}
*{{cite journal  | author=Masson LF, Sharp L, Cotton SC, Little J |title=Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review. |journal=Am. J. Epidemiol. |volume=161 |issue= 10 |pages= 901–15 |year= 2005 |pmid= 15870154 |doi= 10.1093/aje/kwi121 }}
*{{cite journal  | author=Hildebrandt AG, Schwarz D, Krusekopf S, ''et al.'' |title=Recalling P446. P4501A1 (CYP1A1) opting for clinical application. |journal=Drug Metab. Rev. |volume=39 |issue= 2-3 |pages= 323–41 |year= 2007 |pmid= 17786624 |doi= 10.1080/03602530701498026 }}
}}
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{{Cytochrome P450}}

[[Category:Cytochrome P450]]

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[[es:CYP1A1]]
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